US 2010.0015184A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0015184A1 Tue (43) Pub. Date: Jan. 21, 2010 (54) METHODS OF MAKING PHARMACEUTICAL Publication Classification COMPONENTS FOR CUSTOMIZED DRUG PRODUCTS (51) Int. Cl. A6IR 9/00 (2006.01) (76) Inventor: Stephen M. Tuel, Columbia, SC (52) U.S. Cl. ........................................................ 424/400 (US) (57) ABSTRACT Correspondence Address: Methods and systems for developing and manufacturing STPKALA LLC componentized drug product precursor modules that can be 5401 NETHERBYLANE, SUITE 102-A simply assembled to create customized drug products are NORTH CHARLESTON, SC 29420 (US) disclosed. Each module contains components of a final drug product (e.g., active pharmaceutical ingredients, nutritional (21) Appl. No.: 12/518,311 ingredients, and/or excipients) in a fixed mixture selected to maximize desired pharmaceutical characteristics (e.g., stabil (22) PCT Fled: Dec. 13, 2007 ity, manufacturing efficiency) and minimize cost. The mod ules can be extensively tested for quality and assembled immediately, or at a later time, in multiple combinations to (86) PCT NO.: PCT/US2007/025430 customize the final drug product characteristics (e.g., mul tiple active ingredients, doses, flavor, Viscosity, etc.) to meet S371 (c)(1), individual patient/consumer needs and/or preferences while (2), (4) Date: Jun. 9, 2009 assuring high quality. Permitted combinations may be main tained in a database to enable networked drug product selec Related U.S. Application Data tion, prescribing, and ordering. Each resulting customized (60) Provisional application No. 60/874,554, filed on Dec. drug product dose can be labeled to facilitate compliance and 13, 2006. reduce the number of drug products administered per day. Patent Application Publication Jan. 21, 2010 Sheet 1 of 7 US 2010/0015184 A1 Figure 1 AP module dose selection Search public clinical, medical, and health literature, especially pediatric, geriatric, and metabolic disease areas Defined minimum and maximum No License or Create additional doses, minimum escalation proprietary dose knowledge interval dose Convert, as necessary, relative doSeS to absolute doses Minimum dose is ultiple of escalation interva NO Analysis of clinical use, market Or ViceVersa demand, and total dosing range Select greatest common factor or Smaller of minimum Minimum dose dose and escalation interval is greater than escalation interval Select minimum dose as API module dose Select escalation interval as API module dose N Broad total dosing range O Develop one API module dose YeS manufacturingMarket and analysis Develop two API module doses Patent Application Publication Jan. 21, 2010 Sheet 2 of 7 US 2010/0015184 A1 Figure 2 API module excipient selection N Liquid formulation O Available public Available public or proprietary data on API gr proprietary data on granulg solubility formulation License/create additional formulation knowledge Add Solubilizers, Develop simplified antioxidants, pH modifiers coated granules; only if absolutely necessary binder it sustained release characteristics Avoid flavors, Sweeteners, Colors, or viscosity agents Minimize granule size Use aseptic process to avoid antiseptics/preservatives Minimize liquid volume Goal is minimum number of excipients Patent Application Publication Jan. 21, 2010 Sheet 3 of 7 US 2010/0015184 A1 Figure 3 Excipient module component selection Liquid formulation N YeS Taste-masking module N Compare volumes of Solid dose AP module portfolio with Select portfolio of sweet and non total Volumes of final Sweet flavors; add Sweeteners, other formulation options taste-masking agents as needed Select limited number of target Colorant module volumes for "filler modules Develop limited number of color Com ponents with maximum compatibility Select physical components of modules Viscosity module No Develop limited number of viscosity agents with maximum compatibility Develop limited number of preservative modules with maximum compatibility Goal is minimum number of excipient modules with maximum flexibility of combinations Patent Application Publication Jan. 21, 2010 Sheet 4 of 7 US 2010/0015184A1 Figure 4 Module portfolio management Potential new AP module DOSe?cOncentration inside range of existing modules Select dose Select (see Fig. 1) excipients ASSess analytical, (see Fig. 2) formulation, and manufacturing issues Need for new excipient module(s Potential new excipient module Change in Components alters need for new module(s Select excipient module components (see Fig. 3) Additional opportunities to use module Change in Reassess market, Components creates new Opportunities business factors Go/NoGo decision Patent Application Publication Jan. 21, 2010 Sheet 5 of 7 US 2010/0015184 A1 Figure 5 Module selection for final assembly Select first API module type Select number of AP modules Select next AP to provide a dose based on user's physical and clinical module type measures, age, species/breed, or other characteristics Additional AP Liquid No needed formulation Select compatible Select final Compatible taste-masking AP module product form and Yes available module(s) size, e.g., Capsule Select compatible Colorant, viscosity, Select number and/or preservative of excipient modules as needed (filler) modules All needed modules available Forward need for additional modules to R&D Assemble into final product or package for later assembly Patent Application Publication Jan. 21, 2010 Sheet 6 of 7 US 2010/0015184 A1 Figure 6 Final assembly options AP Excipient module module portfolio portfolio Modules for final product Consumer assembly assembly immediate assembly Manual or Manual Or automated process automated process Patent Application Publication Jan. 21, 2010 Sheet 7 of 7 US 2010/0015184 A1 Figure 7 Quality control and ordering processes Public chemical, pharma Ceutical, medical, an veterinary information Module design Batch manufacturing 1N License/Create of modules proprietary ga information Quality and stability testing Module assembly Permitted Combinations database/ordering application Physician, Veterinarian, or Other health professional US 2010/00151.84 A1 Jan. 21, 2010 METHODS OF MAKING PHARMACEUTICAL 0007. In some embodiments, the present invention COMPONENTS FOR CUSTOMZED DRUG includes a method and system for developing and manufac PRODUCTS turing componentized drug product precursor modules that can be simply assembled to create customized drug products. CROSS REFERENCE TO RELATED Some precursor modules of the present system contain two or APPLICATIONS more components of a final drug product in a fixed mixture selected to maximize desired pharmaceutical characteristics 0001. This application claims benefit of priority under and minimize cost. The modules are divided into two classes: PCT Chapter I, Article 8, and 35 U.S.C. S 119(e) of U.S. 1) modules containing an active pharmaceutical ingredient or Provisional Application No. 60/874,554, entitled “Method of specific nutritional ingredient (hereafter called API), and 2) Making Pharmaceutical Components for Assembly of Cus modules containing only excipients. tomized Drug Products.” filed on Dec. 13, 2006, which is 0008. The modules can be extensively tested for quality incorporated herein by reference. and assembled in multiple predetermined combinations, cus tomizing the final drug product characteristics to meet TECHNICAL FIELD patient/consumer needs and/or preferences while assuring 0002 This invention relates to methods and systems for high quality. Permitted combinations can be maintained in an developing and manufacturing componentized drug product Internet-linkable computer database to enable networked precursor modules that can be assembled to create custom drug product selection, prescribing, and ordering. The result ized drug products. ing customized drug product can facilitate compliance and reduce the number of drug products administered per day. BACKGROUND ART 0009. Some embodiments of the present invention provide an API module, comprising: at least one excipient in a first 0003 Pharmaceutical products for use in humans or ani fixed amount, and at least one active pharmaceutical ingredi mals are produced primarily in two ways. High Volume or ent in a second fixed amount of at least a dose escalation high priced drugs are manufactured under very tightly con interval or a fraction thereof. In other embodiments, the sec trolled conditions with detailed specifications, quality test ond fixed amount can be greater than the dose escalation ing, and documentation. Because of the high cost and com interval. In still other embodiments, the second fixed amount plexity of this type of pharmaceutical manufacturing, low can be less than a dose of the at least one active pharmaceu Volume, highly specialized drugs are produced in a cottage tical ingredient. Additional embodiments provide the second industry of compounding pharmacies. These pharmacies mix fixed amount being less than the minimum dose of the at least various active ingredients and excipients into an often unique one active pharmaceutical ingredient. In yet other embodi product based on a doctor's prescription. The specifications, ments, methods for making at least one API module are quality testing, and documentation are often minimal or non provided. Such methods comprise, in some embodiments, existent. Fully testing these products for quality can be cost isolating a first fixed amount of a first API, combining the first prohibitive because of the